The vexed question of MTX and COVID vaccine – ACR Town Hall addresses this and other questions around some of their more contentious COVID vaccine guidelines.
The American College of Rheumatologists (ACR) has released COVID vaccine guidelines for rheumatic disease patients, raising questions from clinicians about the thinking behind some of the recommendations.
To address these concerns the ACR hosted an online Town Hall yesterday with members of its COVID-19 Practice and Advocacy Task Force to talk through the rationale behind the more contentious points, including methotrexate and abatacept withholding time frames, flares, antibody testing and more.
The Task Force was clear on the need to extrapolate in order to provide meaningful guidance, according to Dr Jeffrey Curtis, lead author of the recommendations and chair of the ACR COVID-19 Vaccine Clinical Guidance Task Force.
“Given the lack of direct evidence for these vaccines in rheumatology patients, the panel applied general immunologic principles observed with other vaccines to make recommendations on how to increase the likelihood of a favourable vaccine response,” said Dr Curtis in a press release.
Methotrexate withholding
The ACR recommends withholding MTX in stable RA patients for one week after administering the COVID vaccine. However, for the influenza vaccine it recommends withholding MTX for two weeks after – so why only one week for the COVID vaccine?
The reasoning behind the recommendation is that mRNA COVID vaccines (which are the only ones currently approved in the US) act faster to provide protection. There was also concern that withholding MTX for two weeks for each of two COVID vaccine doses would mean four weeks without MTX, with potential for unacceptable flare risk.
Abatacept withholding
The ACR has also recommended withholding subcutaneous abatacept one week before and one week after the first COVID-19 vaccine dose in patients with stable RA, but with no such precautions the second dose. Intravenous abatacept got similar treatment.
This bore particular scrutiny, not only because of abatacept’s popularity in the US, but also because it has not been singled out for different treatment in other vaccination guidelines, including recent British Society for Rheumatology guidance for COVID-19 vaccinations.
In the town hall, the rationale was revealed: as opposed to other vaccines, which might rely on reactivating memory T cells, COVID-19 vaccines are more dependent on naive T cell activation during the first vaccine dose, but less so during the second. The importance of T cell co-stimulation was enough for the working group to issue moderate strength recommendations surrounding timing of abatacept around the first dose.
Risk of flares
There were concerns that the reactogenic adjuvant in the COVID-19 vaccine could trigger flares while also triggering the immune response — a potential nightmare for Australian rheumatologists as rheumatology patients get vaccinated en masse during stage 1b of Australia’s planned rollout.
The panel reasoned that the current COVID vaccines evoke a specific response, and by extrapolating trial data determined that the risk is very low. While it’s very much a case of watch this space with pharmacovigilance exercises in progress, at this point it seems that the real benefit of the vaccine outweighs uncertain risk.
“Although there is limited data from large population-based studies, it appears that patients with autoimmune and inflammatory conditions are at a higher risk for developing hospitalised COVID-19 compared to the general population and have worse outcomes associated with infection,” said Dr. Curtis in a press release. “Based on this concern, the benefit of COVID-19 vaccination outweighs any small, possible risks for new autoimmune reactions or disease flare after vaccination.”
Antibody testing
There’s concern that rheumatology medications may stop the COVID vaccine from ‘sticking’ – so can you check for antibodies after the vaccine to make sure it’s worked? Not really, at least with current assays which are designed to pick up COVID antibody proteins rather than the coronavirus spike. However, there’s no established correlation between levels of antibodies and protection against COVID: people with antibodies still get infected, while an absence of antibodies doesn’t mean people aren’t protected.
What’s next?
The ACR has submitted to Arthritis & Rheumatology a peer-reviewed manuscript with additional details on the clinical studies, data and discussion points that influenced the recommendations for publication next month.
ACR emphasises that the recommendations are a living document, and will be regularly updated as new information comes to hand.
It also notes that the recommendations should not replace clinical judgement, and decisions about individual patients should consider the patient’s underlying health issues, disease activity level, current treatments and risk of exposure to COVID-19. It’s also important that vaccinated patients continue to follow public health guidelines regarding mask wearing, physical distancing and other preventive measures.
